CA1

Chr 8

carbonic anhydrase 1

Also known as: CA-I, CAB, Car1, HEL-S-11

Carbonic anhydrase 1 is a cytosolic zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide, participating in acid-base balance, respiration, and formation of cerebrospinal fluid. Mutations cause carbonic anhydrase I deficiency, which follows autosomal recessive inheritance and typically presents with mild hemolytic anemia and distal renal tubular acidosis. The gene shows tolerance to loss-of-function variants (high LOEUF score), consistent with the generally mild clinical phenotype.

Summary from RefSeq, UniProt
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1
Active trials
1311
Pubs (1 yr)
32
P/LP submissions
6%
P/LP missense
1.68
LOEUF
DN
Mechanism· predicted
Clinical SummaryCA1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 38 VUS of 80 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — CA1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.68LOEUF
pLI 0.000
Z-score -0.38
OE 1.11 (0.741.68)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.21Z-score
OE missense 1.05 (0.921.21)
143 obs / 136.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.11 (0.741.68)
00.351.4
Missense OE1.05 (0.921.21)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 15 / 13.5Missense obs/exp: 143 / 136.1Syn Z: -0.56
DN
0.6839th %ile
GOF
0.5071th %ile
LOF
0.3068th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

80 submitted variants in ClinVar

Classification Summary

Pathogenic32
VUS38
Likely Benign2
Benign4
32
Pathogenic
38
VUS
2
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
30
0
32
Likely Pathogenic
0
0
0
0
0
VUS
1
29
8
0
38
Likely Benign
0
1
1
0
2
Benign
0
3
0
1
4
Total13539176

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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